Background: Clinical
trials investigating the effects of addition of oxaliplatin to neoadjuvant radiochemotherapy
in locally advanced rectal cancers (LARC) have brought controversial results for
pathologic complete response as an endpoint.

Aim: This phase III randomized study investigated downstaging as a short term surrogate for progression free survival (PFS).

Methods: Patients
with MRI defined T3, T4 or N+ histologically proven adenocarcinoma of rectum
within 15 cm from anal verge were randomly assigned to receive 50-50.4 Gy external
beam radiation in 25-28 fractions and concurrent capecitabine 825 mg/m2 twice
daily 5 days a week with or without oxaliplatin 60 mg/m2 weekly as neoadjuvant radiochemotherapy
(capox and cap group respectively). T and N downstage were defined as at least
one stage regression in pathologic report after surgery comparing to MRI image
before the pre-operative treatment. Adverse effects of treatment were recorded
on a weekly basis according to National Cancer Institute Common Toxicity
Criteria, version 4.

Results: 63
patients were randomly assigned to cap (n=31) and capox (n=32) groups. There was
no grade 4 toxicity. The only grade 3 toxicity which occurred more in capox group
was diarrhea (21.87% vs 0%; p=0.006) . Histopathologic stage of 52 patients (27
patients in cap and 25 patients in capox groups) were compared to their
preoperative stage defined by MRI. There was a greater rate of T downstage in capox
group (59.37% vs 41.93%; p=0.037). The N downstage occurred non-significantly more
in capox group (62.5% vs 51.6%; p=0.424). 11 patients in capox group (34.37%)
achieved pathologic complete response, comparing to 4 in cap group (12.9%); p=0.072.

Conclusions: The
addition of oxalipatin to neoadjuvant radiochemotherapy in LARC led to higher
rate of tumor downstaging. Longer follow up is needed to evaluate PFS.